Do high serum levels of anti-Saccharomyces cerevisiae antibodies result from a leakiness of the gut barrier in Crohn's disease?

Objectives: To examine the relationship between serum levels of anti-Saccharomyces cerevisiae antibodies (ASCAs) and intestinal permeability at a given time (hypothesis 1) and the probability of increased ASCA serum levels with increased intestinal permeability (hypothesis 2) in patients with Crohn's disease.

Methods: Each hypothesis was tested retrospectively with its own study population: group A for hypothesis 1 and group B for hypothesis 2. Intestinal permeability was measured by lactulose/mannitol test and ASCAs were quantified by using ELISA. Patients received either no treatment or 5-aminosalicylates. The lactulose/mannitol test and sampling of sera for ASCA assessment had to be performed within 1 month in group A. In group B the highest intestinal permeability value obtained from among at least three measurements made during different stages of disease activity was chosen for evaluation.

Results: Both study populations consisted of 140 patients with Crohn's disease. Elevated IgG ASCAs were detected in 64% (90/140) in group A compared with 65% (91/140) in group B. In group A, 64% (90/140) and in group B 66% (92/140) were IgA ASCA positive. Correlation analysis showed a tendency for a positive relationship between IgG ASCAs and intestinal permeability in group A (tau = 0.16, P = 0.07) and in group B (tau = 0.16, P = 0.06). A positive trend was seen for the combination of high intestinal permeability and high IgG ASCAs in group B (chi-squared test, P = 0.07).

Conclusion: Elevated serum levels of anti-S. cerevisiae antibodies do not seem to result primarily from a defect of the gut barrier. This observation points to an intrinsic pathomechanism in the development of increased ASCA serum levels.